Fluoroquinolones are antibiotics obtained by chemical synthesis exhibiting a wide antibacterial spectrum. These compounds inhibit topoisomerase II or DNA gyrase and thus the replication and the transcription of the DNA of bacteria.
As examples of fluoroquinolones, mention may be made in particular of lomefloxacin, ciprofloxacin, norfloxacin and pefloxacin, the structures of which are represented below.
                lomefloxacin: Ra=ethyl, Rb=3-methyl-1-piperazinyl, Rc=F; ciprofloxacin: Ra=cyclopropyl, Rb=1-piperazinyl, Rc=H; norfloxacin: Ra=ethyl, Rb=1-piperazinyl, Rc=H; pefloxacin: Ra=ethyl, Rb=4-methyl-1-piperazinyl, Rc=H.        
Several methods of synthesis of these compounds are reported in the literature (U.S. Pat. No. 4,146,719; FR 2 555 584; Hiroshi Koga et al, J. Med. Chem., 1980, 23, 1358-1363; Domagala et al, J. Med. Chem., 1991, 34, 1142-1154). These methods generally involve the implementation of two steps, including in particular a step a) of carboxylic ester hydrolysis (3) into the corresponding acid (2) followed by a step b) of nucleophilic substitution of a halogen atom, in particular Cl or F, by a precursor agent of the group Rb, in particular a piperazinyl derivative, by which the desired fluoroquinolone (1) is obtained (Diagram I). The two chemical reactions of hydrolysis and substitution can also be implemented in reverse order, nucleophilic substitution of the halogen nucleus then hydrolysis of the ester.

Step b) is generally carried out in the presence of an organic solvent such as pyridine or acetonitrile at reflux, or also DMF, optionally in the presence of an organic base such as triethylamine (Domagala et al, J. Med. Chem., 1991, 34, 1142-1154).
A method of preparation of fluoroquinolones involving a step b) in water has recently been reported in the literature (M. Saeed Abaee et al, Heterocyclic Communications, Vol. 11, No. 5, 2005). However, this reaction is accompanied by the formation of a substantial quantity of position isomer. Moreover, it is necessary to heat the reaction medium for several hours at a high temperature.
A novel method has now been developed for preparation of fluoroquinolones in a limited number of steps. More specifically, according to this method, steps a) and b) above are advantageously carried out in one single step.
Moreover, this method is carried out in water which constitutes a considerable economic and ecological advantage.
Finally, this method enables access to variously substituted fluoroquinolones with high yields and a level of purity. Advantageously, the method according to the invention makes it possible to obtain yields higher than 90% and even higher than 96%.